Macrovascular Complication in

Diabetes Mellitus
Hadi Purnomo

PENDAHULUAN
Diabetes kini merupakan masalah kesehatan dunia
dengan 137 jt kasus
Peningkatan kasus akan terjadi di negara
berkembang dengan laju peningkatan 200 %
Diabetes tipe 1 bermanifestasi pada masa kanakkanak dan dewasa dengan gejala berupa penurunan
BB tiba-tiba serta hiperglikemia berat
Diabetes tipe 2 lebih ringan daripada diabetes tipe
1, 80 90 % penderitanya mengalami kegemukan
Kedua tipe diabetes terkait dengan gangguan
jantung, stroke, tekanan darah tinggi, gangguan
ginjal, saraf dan kebutaan

U.S. Hospitalization for

Chronic Complications of Diabetes

Cardiovascular 77%
Other 4%
Ophthalmic 4%
Neurologic 6%
Renal 9%

Diabetes and Increased CV risk

The Framingham Study. JAMA 1988;260;
3456-60. Fatal AMI in men with DM
double. Fatal AMI ini women with DM
quadruple
High out of hospital fatality following first
AMI in men with DM
Therefore diabetic treatment should include
optimal therapy for both of these disease

Aging population more sedentary &

overweight incidence DM
80 % of death cardiovascular disease
75 % Ischemic Heart Disease
DM type I : type II; 2:8
DM twice incidence of ACS 1,5 2 x
death after AMI

Pathophysiology : macrovasc compl.

Vasculopathic state caused by multiple
metabolic derangement :
Hyperglycemia
Hyperinsulinemia
Abberancies of the coagulation system

Associated other risk factors : obesity, old,

hypertention

Hyperinsulinemia premature atherosclirotic

disease A weak independent risk factor
Dyslipidemia : high VLDL & total Triglycerides
decreased HDL
Elevated LDL : smal dense
glycation of LDL
Coagulation System :
Platelet function tromboxane A2
Reduction in life span von Willebrand factor
fibrinogen, d.driver, thrombin PAI-I and activity factor
VIII

Associated factors
Changes in vasoreactivity
No production and action
No scavenging
Blunted vasomotor reactivity caused by microvascular
atherosclerosis

Neuropathic changes autonomis neuropathy

unopposed sympathetic tone plague instability
ACS, arrhytmogenicity, CHF
Sensoryneuropathy atypical chest pain
delanged to hospital
Altere anaerobic mechanism : inappropriate free
fatty acid metabolism impair vasoreactivity,
arrhythninogenicity, decrease contractility,
increased infarct size

Mortality after acute coronary syndrome in

diabetic patient still high compare to non DM
Insulin anaerobic metabolism
To reverse this derrangement with GIK
therapy
Ischemic preconditioning
The used of anti glycemic drugs?

Suggested Therapy
FLUIDS
INSULIN
POTASSIUM
BICARBONATE

Type-2 Diabetes and Coronary

Artery Disease
People with Type-2 DM have an increased risk of
dying prematurely compared to non-DM :
High mortality rate after AMI

Acute rate is increased 2-3 times

Persists in thrombolytic studies
DM-specific factors responsible

Worse 5-year revascularization

Postangioplasty : 34% vs 9%
Post-CABG : 19% vs 9%

High long-term mortality

60

Diabetic
NonDiabetic

50

Mortality (%)

40

P < 0.001

30
20
10
0

1
5

Duration of follow up
(years)
Five-year mortality among diabetics and non diabetics during
follow up after myocardial infarction
Herlitz J Acta Med Scand
1988

10

Diabetic
NonDiabetic

0
90

Survival (%)

80
70
60
50
40
30
0

1
5

Duration of follow up
(years)
Survival rates for diabetic and non-diabetic subjects aged 65
years or more,with angiographicaly proven CAD
Barzilay JL et al Am J Cardio
1994;74:334-9

Diabetes and Coronary Artery Disease

%
14
12
10
8
6
4
2

HbA1c >9.8
HbA1c <9.8

0
< 6 years

7 years

Duration of diabetes

The 3.5-year incidence (%) of CHD death with respect to the

median of HbA1c and duration of diabetes.Kuusisto et al Diabetes 43;960-967, 1994

Diabetes and Coronary Artery Disease

Type-2 Diabetes
Macrovascular complication
2 3 times higher than non diabetic
High prevalence of cardiovascular complications
at diagnosis

Weakly related to the

duration of the diabetes

Occurs before diabetes develops (IGT)

Insulin resistance syndrome

Coronary Mortality in Diabetic

and Non Diabetic Men
80

60

Diabetic

40

20
10

Non Diabetic

0
4

Serum cholesterol (mmol/L)

10 year CHD mortality per 1000

10 year CHD mortality per 1000

80

60
Diabetic

40

20
10

Non Diabetic

0
110

120

130

140

150

160

Systolic blood pressure (mmHg)

Stamler et al Diabetes Care 16:434-444, 1

D
P
UK
S

Conclusion of Blood Pressure Control

Study
The UKPDS has shown that tight blood
pressure control reduces the risk of
diabetic macro and microvascular
complications

Coronary Angiography in Diabetic Patients

1. Diabetes is associated with more severe

atherosclerosis of the coronary vessels
independently of other risk factors
2. The effect of diabetes on coronary atherosclerosis
is greater in women than in men
3. Coronary atherosclerosis explains the higher cardiac
mortality of diabetic patients
4. Diabetic patients without PMI (previous myocardial
infarction) have a similar degree of coronary
atherosclerosis and mortality rates as non-diabetic
patients with PMI
5. Proteinuria is not by itself a marker of coronary
atherosclerosis but does identify, especially in
diabetic people, a subgroup of patients at high risk
of cardiac death
Natali A et al Diabetologia 2000;43:632-6

eterlibatan Disfungsi Endotel pada Penyakit Kardiovaskul

Faktor risiko

Disfungsi endotel

Akibat

Hemodinamik (shear
stress tekanan)

Vasospasme
Hipertensi
DIABETES

PGI2

PGH2/ TXA2

Lipd (ox-LDL)
Hipoksia

Trombosis
EDRF (NO)

ET-1

Infeksi (virus/bakteri)
Kelainan imun (allograf)
Rokok

Ateroskleros

Approaches for Risk Reduction

in Type-2 Diabetic Patients
Stop smoking
Optimize diabetes control
Screen and treat hyprtension
Screen and treat dyslipidemia
Give dietary advice
Optimizing diabetes control
Maintaining ideal body weight
Lowering lipids

Encourage aerobic exercise

Schernthaner G
1996

Kesimpulan
Diabetes jelas merupakan faktor risiko PJK
yang independen
Makin tinggi kadar HbA1c makin tinggi
kemungkinan mendapat PJK
Korelasi kadar glukosa darah pp lebih baik
dibanding dengan puasa dalam kaitannya
dengan PJK (belum ada EBM)
Kelainan vascular pada diabetes lebih
banyak bermakna pada kelainan multi vessel
Hubungan antara lamanya diabetes dengan
prevalensi PJK tidak cukup kuat

Thank you